Vitamin B12 and cardiovascular health: mechanisms, clinical evidence, and future directions

Cardiovascular disease (CVD) continues to be the primary cause of morbidity and death globally. New research shows that vitamin B₁₂ is very important for vascular health since it controls homocysteine metabolism, endothelial function, and one-carbon pathways. Deficiency not only causes hyperhomocysteinemia, oxidative stress, and vascular damage, but it also affects epigenetic pathways associated with atherosclerosis. Certain groups of people are more likely to have cardiovascular problems because of deficiencies. These groups include the elderly, vegetarians and vegans, people who have had bariatric surgery, those with chronic renal illness, and pregnant women. This review integrates information from mechanistic, epidemiological, and interventional investigations. Sources include experimental models, extensive cohort studies, and randomized controlled trials evaluating vitamin B₁₂ status, biomarkers (holotranscobalamin, methylmalonic acid), and cardiovascular outcomes. Observational studies consistently associate decreased vitamin B₁₂ levels with elevated risks of atherosclerosis, stroke, arrhythmia, and heart failure. Supplementation consistently reduces homocysteine levels; nevertheless, randomized studies have variable impacts on cardiovascular events, with advantages mostly seen in select populations, especially in countries lacking folate fortification and in stroke prevention. Advanced biomarkers, especially holotranscobalamin and methylmalonic acid, improve the detection of functional vitamin B₁₂ deficiency but remain limited in predicting cardiovascular endpoints. Combined B-vitamin treatment has more pronounced biochemical benefits, although it exhibits variable clinical applicability. Vitamin B₁₂ has several effects on heart health; however, taking it as a supplement has not always led to widespread clinical benefits. Strategies based on precision that combine biochemical, nutritional, and genetic screening may assist in identifying high-risk individuals who are most likely to benefit. Genetic information may have future value for research-based risk stratification, but current evidence does not support routine genetic screening for vitamin B₁₂ deficiency or cardiovascular prevention. Subsequent research needs to concentrate on population-specific effects, biomarker-directed screening, and tailored supplementation to reconcile the disparity between molecular potential and clinical results. Not applicable.